Skip directly to site content Skip directly to page options Skip directly to A-Z link Skip directly to A-Z link Skip directly to A-Z link
Volume 16, Number 3—March 2010
Letter

Two Lineages of Dengue Virus Type 2, Brazil

On This Page
Figures
Altmetric
34
citations of this article
EID Journal Metrics on Scopus

Cite This Article

To the Editor: Dengue viruses (DENVs) belong to the genus Flavivirus (family Flaviviridae) and exist as 4 antigenic types, serotypes 1–4, each with well-defined genotypes. Dengue virus is associated with clinical manifestations that range from asymptomatic infections and relatively mild disease (classic dengue fever) to more severe forms of dengue hemorrhagic fever and dengue shock syndrome. Dengue has become one of the most serious vector-borne diseases in humans. The World Health Organization estimates that 2.5 billion persons live in dengue-endemic areas and >50 million are infected annually (1).

In 1986, dengue virus type 1 (DENV-1) caused an outbreak in the state of Rio de Janeiro and has since become a public health concern and threat in Brazil. (2). In 1990, DENV-2 was reported in the state of Rio de Janeiro, where the first severe forms of dengue hemorrhagic fever and fatal cases of dengue shock syndrome were documented. The disease gradually spread to other regions of the country (3). In 2002, DENV-3 caused the most severe dengue outbreak in the country and sporadic outbreaks continued to be documented through 2005 (4).

Since 1990, two additional epidemics caused by DENV-2 have occurred (1998 and 2007–2008) in Brazil. A severe DENV-2 epidemic in the state of Rio de Janeiro began in 2007 and continued in 2008; a total of 255,818 cases and 252 deaths were reported (5). This epidemic prompted us to investigate the genetic relatedness of DENV-2 for all of these epidemics.

Figure

Thumbnail of Neighbor-joining phylogenetic tree of 68 complete envelope (E) gene sequences of dengue virus type 2 (DENV-2). Only bootstrap values >80% are shown. DENV-2 sequences obtained from 21 patients infected during the 1990, 1998, and 2007–2008 epidemics were isolated from acute-phase cases. Viral RNA was extracted from 140 µL of serum or supernatant of infected C636 cell cultures by using the QIAamp Viral RNA Mini Kit (QIAGEN, Valencia, CA, USA), and cDNA synthesis was performed by usi

Figure. Neighbor-joining phylogenetic tree of 68 complete envelope (E) gene sequences of dengue virus type 2 (DENV-2). Only bootstrap values >80% are shown. DENV-2 sequences obtained from 21 patients infected during the...

DENV-2 isolates from these epidemic periods were subjected to sequencing and comparison. Gross sequences of DENV-2 isolates from all epidemic periods grouped with sequences from DENV-2 American/Asian genotype; this finding was expected because this genotype is circulating in the Americas (6,7). Sequences of DENV-2 isolates from the 1998 epidemic grouped with sequences of DENV-2 isolates from the 1990 epidemic (data not shown) suggesting that viruses circulating during these 2 epidemic periods belong to the same lineage of the DENV-2 strain originally found in the state of Rio de Janeiro. However, sequences of DENV-2 isolates from 2007/2008 epidemics grouped separately and distinctly from the 1990 and 1998 DENV-2 isolates and represented a monophyletic group in the phylogenetic tree with bootstraps of 98% (Figure). This result shows a temporal circulation of genetically different viruses in Rio de Janeiro that could be a result of local evolution of DENV-2 since its introduction in 1990, or even an introduction of a new lineage of DENV-2 in the region.

A study conducted by Aquino et al. (7) showed that Paraguayan DENV-2 strains could be grouped as 2 distinct variants within the American/Asian genotype, thus further supporting that the introduction of new DENV-2 variants may likely associate with the shift of dominant serotypes from DENV-3 to DENV-2 in 2005 and might have caused an outbreak of DENV-2. Our results are consistent with this scenario because was a shift of a dominant serotype from DENV-3 to DENV-2 that was observed in 2008 in Rio de Janeiro. However, other factors, such as immunity level to DENV-3 and DENV-2, could explain the shift of dominant serotype besides the circulation of a new viral variant.

Because the dengue outbreaks of 2007 and 2008 were the most severe of the dengue infections in Brazil in terms of number of cases and deaths, this genetically distinct DENV-2 could have contributed to this pathogenic profile. Additionally, these samples came from disperse locations in Rio de Janeiro and we do not believe that there is a clustering issue in our sampling. However, again, other factors must be considered as contributors to this scenario because of the intrinsic properties of this distinct virus, host susceptibility, and secondary cases of infection.

In addition, detailed examination of amino acid sequences of Brazilian DENV-2 strains isolated in 1998 and 2008 showed 6 aa substitutions in the envelope gene: V129I, L131Q, I170T, E203D, M340T, and I380V. Our results support the notion that aa positions at 129 and 131 in the envelope gene are critical genetic markers for phylogenetic classification of DENV-2 (79).

Notably, residue 131 in the envelope gene is located within a pH-dependent hinge region at the interface between domains I and II of the envelope protein. Mutations at this region may affect the pH threshold of fusion and the process of conformational changes (10).

Our results suggest the circulation of genetically different DENV-2 in Brazil and that these viruses may have a role in severity of dengue diseases. These findings can help to further understand the complex dynamic pathogenic profile of dengue viruses and their circulation in dengue-endemic regions.

Top

Michelli Faria Oliveira1, Josélio Maria Galvão Araújo1, Orlando Costa Ferreira, Davis Fernandes Ferreira, Dirce Bonfim Lima, Flavia Barreto Santos, Hermann Gonçalves Schatzmayr, Amilcar TanuriComments to Author , and Rita Maria Ribeiro Nogueira

Author affiliations: Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil (M.F. Oliveira, O. Costa Ferreira Jr., D.F. Feirreira, A. Tanuri); Instituto Oswaldo, Rio de Janeiro (J.M.G. Araújo, F.B. Santos, H.G. Schatzmayr, R.M. Ribeiro Nogueira); Universidade do Estado do Rio de Janeiro, Rio de Janeiro (D.B. Lima)

Top

References

  1. World Health Organization (WHO). Impact of dengue [cited 2009 Feb 25]. http://www.who.int/csr/disease/dengue/impact/en/index.html
  2. Schatzmayr  HG, Nogueira  RM, Travassos da Rosa  AP. An outbreak of dengue virus at Rio de Janeiro-1986. Mem Inst Oswaldo Cruz. 1986;81:2456. DOIPubMed
  3. Nogueria  RM, Miagostovich  MP, Lampe  E, Souza  RW, Zagne  SM, Schatzmayr  HG, Dengue epidemic in the stage of Rio de Janeiro, Brazil, 1990–1: co-circulation of dengue 1 and dengue 2 serotypes. Epidemiol Infect. 1993;111:16370. DOIPubMed
  4. Nogueira  RM, Schatzmayr  HG, Filippis  AM, Santos  FB, Cunha  RV, Coelho  JO, Dengue type 3, Brazil, 2002. Emerg Infect Dis. 2005;11:137681.PubMed
  5. Secretaria de Vigilância em Saúde (SVS). Relatório de casos de dengue–2008. 2009 [cited 2009 Feb 25]. http://www.saude.rj.gov.br/Docs/Acoes/dengue/Dengue/Relat%C3%B3rio%20de%20Casos%20de%20Dengue%20_18–02–2009%20-%2019h25m_%20-%202008.pdf.
  6. Twiddy  SS, Farrar  JJ, Vinh Chau  N, Wills  B, Gould  EA, Gritsun  T, Phylogenetic relationships and differential selection pressures among genotypes of dengue-2 virus. Virology. 2002;298:6372. DOIPubMed
  7. Aquino  JD, Tang  WF, Ishii  R, Ono  T, Eshita  Y, Aono  H, Molecular epidemiology of dengue virus serotypes 2 and 3 in Paraguay during 2001–2006: the association of viral clade introductions with shifting serotype dominance. Virus Res. 2008;137:26670. DOIPubMed
  8. Bennett  SN, Holmes  EC, Chirivella  M, Rodriguez  DM, Beltran  M, Vorndam  V, Molecular evolution of dengue 2 virus in Puerto Rico: positive selection in the viral envelope accompanies clade reintroduction. J Gen Virol. 2006;87:88593. DOIPubMed
  9. Modis  Y, Ogata  S, Clements  D, Harrison  SC. A ligand-binding pocket in the dengue virus envelope glycoprotein. Proc Natl Acad Sci U S A. 2003;100:698691. DOIPubMed
  10. Modis  Y, Ogata  S, Clements  D, Harrison  SC. Structure of the dengue vírus envelope protein after membrane fusion. Nature. 2004;427:3139. DOIPubMed

Top

Figure

Top

Cite This Article

DOI: 10.3201/eid1603.090996

1These authors contributed equally to this article.

Related Links

Top

Table of Contents – Volume 16, Number 3—March 2010

Comments

Please use the form below to submit correspondence to the authors or contact them at the following address:

Amilcar Tanuri, Laboratório de Virologia Molecular Animal, Departamento de Genética – Instituto de Biologia, Universidade Federal do Rio de Janeiro, CCS, Bloco A, sala 121, Av: Brigadeiro Trompowski, s/n, Ilha do Fundão, Rio de Janeiro, CEP 21944-970, RJ, Brazil

Send To

character(s) remaining.

Comment submitted successfully, thank you for your feedback.

Top

Page created: December 14, 2010
Page updated: December 14, 2010
Page reviewed: December 14, 2010
The conclusions, findings, and opinions expressed by authors contributing to this journal do not necessarily reflect the official position of the U.S. Department of Health and Human Services, the Public Health Service, the Centers for Disease Control and Prevention, or the authors' affiliated institutions. Use of trade names is for identification only and does not imply endorsement by any of the groups named above.
file_external